Three aspects of alpha-fetoprotein (AFP) - the fetal protein associated with hepatoma teratomas and some other tumors will be studied: 1. Chemical characterization including sequencing will be continued. We have previously determined the N-terminal sequence of human AFP and will also determine N-terminal sequence of some of its cyanogen bromide fragments. Peptides will be synthesized on the basis of sequence information. 2. New immunoassays based on these peptides and their antibodies will be set up. Such an assay can perhaps be used to measure AFP in biological samples with greater specificity. This would eliminate the need for AFP purified from fetuses or hepatoma patients' sera. 3. Expression of AFP in spontaneous hepatomas and the application of AFP to immunotherapy and immunoprevention of AFP producing hepatomas will be studied. Recent demonstration of in vitro cytotoxicity of heterologous anti-AFP to AFP producing hepatoma cells and the fact that tolerance to AFP can be broken in experimental animals suggest that this may be possible. Initial studies have shown that mice having serum antibodies to AFP do not have increased resistance towards hepatomas. Current studies aim at production of cellular immunity to AFP. BIBLIOGRAPHIC REFERENCES: Ruoslahti, E., and Engvall, E. Immunological Crossreaction Between Alpha-Fetoprotein and Albumin, Proc. Natl. Acad. Sci., 73:4641 (1976). Attardi, B. and Ruoslahti, E. Foetoneonatal oestradiol - binding protein in mouse brain cytosol is alpha-foetoprotein. Nature, 263-685 (1976).